Very Concerning Article Claiming Keto Diet Causing Afib in Rats and Humans

science

#1

https://www.nature.com/articles/s41392-020-00411-4

I skimmed the article and if it has already been posted, I did not see it. Basically the study is claiming that the Ketones themselves (specifically Beta Hydroxybutyrate) cause some type of mitochondrial downregulation in heart cells (did not fully understand this part have no scientific training) which leads to cardiac fibrosis (thickening of heart muscle making it less effective) and potentially Afib as well.
I read through the methodology section which is a separate download. The rats were fed 62% Cocoa Butter they were NOT fed crappy canola or soybean oil for the most part

Thoughts? Comments? Science? Weakness in the methodology? Again, did not understand most of it so if someone has a better handle on it please let me know


(Vic) #2

Rats are not humans, the whole studie is irrelevant to us.

Rats are a very poor choice for KD research, these animals die very quickly deprived od carbohydrates.

Raising the level of BHB in rats by starving them is not a KD it is No Diet.

There is more, the whole thing is tk ridiculous to read past the abstract

Jm2c :wink:


#3

I never rely only on the abstract if it is a topic I am interested in. The abstract is designed to catch attention and in some cases does not accurately reflect the research and may not have been written by the researcher.

Yes we are not rats, and I really hope someone can scientifically explain why this is not relevant to us. However in the interim I have concerns.

As for this not being relevant to anyone but rats the research states there are negative associations with high ketones in humans:

Blockquote “For example, the concentration of β-OHB in heart tissues is significantly higher in patients with atrial fibrillation (AF).15

While I do have some criticism, for example, I do not think this has been peer reviewed but it raises concerns and I do not have enough knowledge to know if they are valid but the downside is potentially enormous


(Central Florida Bob ) #4

The problem with the association is the “firemen at a fire” association. Are they there because they’re fighting the fire or because they started it? Is the Beta-OHB causing it or repairing the damage they’re talking about? Without cause and effect information you can’t know. I suspect you’ve heard the common argument against the belief that LDL cholesterol causes arterial plaque is that our body is supplying the LDL to repair damage from something else. Same idea.

I’ve read in many places that the heart runs better on Beta Hydroxybutyrate than other fuels. A web search on the phrase, “heart runs better on ketones” turns up lots of interesting links.


and
https://academic.oup.com/cardiovascres/article/114/1/e1/4775035


#5

I sincerely hope you are correct but it does make me hesitate to start fasting again (which I will not do anyway until I am vaccinated because it makes me vulnerable to viruses (speaking from experience)). I really do hope I am concerned for no reason but I simply do not know enough.

Anyone know if any of the Keto Docs and experts have reviewed this and commented?

Well aware of the drowning and ice cream correlation. However it did seem they took healthy rats and gave them Afib and in the reseach prior to this it seemed there was a higher level of BHB in those (Humans) who developed Afib

Here is a link to the relevant underlying research from 2008

https://www.jacc.org/doi/full/10.1016/j.jacc.2007.09.055

" oxidation of ketones as a sole substrate can also lead to cardiac contractile failure (28,31) and increased risk of arrhythmogenesis through accumulation of glycogen (32)"

The relevant sections are the Summary, Clinical Implications, Ketone Bodies in AF and Energy Metabolism, again they are not written for the lay person so if anyone can translate that would be great


(Bacon by any other name would taste just as great.) #6

Animal studies may or may not be relevant to human health. We should not dismiss a study simply because it was done on animals, but rather assess each study on its merits.

In this case, I’d mention a couple of thoughts. First, it is extremely difficult to get rats into ketosis. I corresponded briefly with Peter of the Hyperlipid blog, since he is a veterinarian, and it turns out that most mammals normally only enter ketosis during the late stages of starvation. (This dashed my hopes of extending my pet rats’ lives by putting them on a ketogenic diet.) Human beings are practically unique in being able to enter ketosis so readily.

This difference between rats and people may be relevant here, since the diet needed in order to get rats to make ketones is likely to be very different from a diet that does the same thing for human beings. So I am confused by the authors’ use of the term “ketogenic diet” in this context. It is possible that they are using the term simply to mean some kind of low-carbohydrate, high-fat diet, but I would like to know precisely what it was they fed the rats. Was this diet something that approximates what rats would eat in the wild? If not, that might be relevant. It would also be useful to know the duration of this experiment. (The diet and the duration may have been mentioned in the article; but I didn’t see this information as I skimmed.)

Second, it is entirely possible (though I’m not clear whether this study actually shows it) that too much β-hydroxybutyrate might cause heart damage in rats. On the other hand, Dr. Phinney cites, in a couple of his lectures available on YouTube, a study showing that β-hydroxybutyrate actually benefits the human heart, since it requires less oxygen to metabolise than fatty acids, a clear benefit for muscle served by occluded arteries. Β-hydroxybutyrate has also been shown to have many other benefits in the human body (and so have the other two ketone bodies, acetoacetate and acetone).

Third, I am puzzled by the statement in this article that claims that β-hydroxybutyrate causes damage to mitochondria, since β-hydroxybutyrate is actually produced by the mitochondria as they metabolise fatty acids. Ketone bodies are partial metabolites of fatty acids. When the liver is producing ketones for the rest of the body (ketogenesis), the process stops, and the ketones are distributed for use by cells that can use them. On the other hand, when muscles metabolise fatty acids, they produce ketone bodies midway through the process, which then continues until the ketones are reduced to carbon dioxide and water (much as wood first becomes charcoal as it burns and then is eventually reduced to carbon dioxide and ash).

We know that glucose metabolism can cause mitochondrial damage if the radical oxygen species (ROS) produced overwhelm the defenses against them, but I haven’t heard of similar damage from fatty-acid metabolism. So I suspect that this idea that β-hydroxybutyrate damages the heart may be a misinterpretation of the data, even in rats.

It also concerns me that the authors of the article speak of a ketogenic diet as a reduced-calorie diet. I think they are missing important nuances of how a ketogenic diet affects the human body. Given the difficulties of getting rats into ketosis, I would expect that assuming a ketogenic diet to be energy-deficient could affect how one interprets one’s observations.

Furthermore, I would point out that it can happen that the effects of a substance on cells in vitro may differ from the effects in vivo. The human body has evolved to a level of complexity that can handle most of what gets thrown at it. Cells in isolation can sometimes be affected differently, because they don’t have the full range of bodily processes to protect them. This is not to say that examining cells in vitro is without merit, only that care must be taken when analysing the results.

Lastly, I have to say that I find it highly unlikely that the diet on which the human race is known to have evolved could possibly be harmful. We know from anthropology and archaeology that human societies that eat almost entirely meat are much healthier than societies that adopt a largely plant-based diet.


(Doug) #7

Very good point, Paul. Yes - in this respect rats and humans are substantially different. So, even at the best, I’d say the study needs to be taken with the proverbial grain of salt.

Interesting stuff, Saphire. It does say, under ‘Study limitations’: The heterogeneous nature of AF means that despite the sample size of this study (n = 45) exceeding any previous metabolomic studies using human cardiac tissue samples, the assessment of the impact of different underlying mechanisms on metabolism will require future exploration in larger independent data sets. Furthermore, NMR currently only monitors approximately 20 to 30 of the most abundant metabolites, and the predictive value of absolute metabolite concentrations is hindered by the different pathophysiologies themselves expressing variable metabolic profiles.

I didn’t know there was any talk at all about “ketogenic diets harming the heart.” My gut feeling - which is just from a layman and totally subjective - is that since there are now a lot of people who have been eating ketogenically for a long time, if there really was a substantial problem in this regard, it would have been noted by now.

And perhaps there’s not a simple “yes or no” answer there; perhaps I’m just ‘somewhat wrong’ and some people (who later may be able to be identified by further research) really do have something to be concerned about.

However, I contrast this type of supposition with the pretty darn solid evidence that going keto really does help a lot of people with circulatory system issues. High blood sugar and high insulin definitely do often cause harm over the long term, no?

In my case, it’s impossible for me to think that “keto is bad for me,” versus a high carbohydrate diet.


(Bacon by any other name would taste just as great.) #8

Bingo. While there is plenty of room for individual variation and outlying cases, if keto were bad for the general population, we’d know. And as you say, hyperglycaemia and hyperinsulinaemia are known causes of damage to the human body.


(Michael - When reality fails to meet expectations, the problem is not reality.) #9

BINGO! Once our humanoid ancestors abandoned the big guts of our primate forebears necessary to digest cellulose and other very complex carbohydrates the die was cast. Until the advent of the agricultural revolution of 8K years ago, plants contained too little digestible nutrients to provide more than a very small portion of our ancestors’ food. Consequently, our ancestors spent most of their lives in ketosis. Gluconeogenesis provided the small amount of required glucose. If this had caused severe enough problems we would not be here to talk about it.


#10

I didn’t know there was any talk at all about “ketogenic diets harming the heart.” My gut feeling - which is just from a layman and totally subjective - is that since there are now a lot of people who have been eating ketogenically for a long time, if there really was a substantial problem in this regard, it would have been noted by now.

I WILL HIT THIS WITH ANOTHER BINGO!

same with carnivore, we got zero carb eaters hitting into the 15 yr-20 and more mark and healthy as heck and ‘no rat’ study applies to them so? We all know Keto plan people are out there thriving so?


(Vic) #11

My heart healed on carnivore, to my doctors amazement.

If you feed a rat what I eat:
1 it would not be in ketosis.
2 it would be dead in no time.

The keto diet has been dragged thru the mud by many, such as vegans and Ansel Keys fanboys.
Stupid research like this is very popular, the anti keto crowd can orgasm on a wave of confirmation bias emotions.

I’m not buying it. Humans are obligate carnivores evolved to trive in a state of ketosis.


(Edith) #12

With all of the above excellent points I would add that maybe it could be possible to develop Afib while on a ketogenic diet, particularly if it is not well formulated. A draw down of nutrients and electrolyte troubles could result in heart trouble. That would not be from the ketones but poor nutrition while on the diet.

I developed heart palpitations while following this way or eating, but the answer was in my nutrients.


#13

Very valid point and that was my first reaction until I read the study. The KD rats were being fed better than the control group. Also there was a third rodent group that did alternate day fasting and they had the same problems as I read the study.

I tried to cut and paste but it is a word file and I do not have word. If you go to the Supplemental Materials in the new research it lists the food in the first paragraph. The control rats were being fed the usual crap with corn being a primary ingredient. The KD rats actually had a diet that was 62% Cocoa Butter.

You have a point although lots of causalities are not known until years later, smoking anyone?! Also even with smoking not everyone was affected. My grandmother who lived to 98 smoked from 16 - 78 and was traveling until her 90s, no COPD or even a cough

I think that they mention the reduced calorie as a way to close a loophole. Since the KD rats did lose weight, they did not want the study results obscured by the weight loss aspect or demonstrating that calorie restriction caused the problems. That is why they put a third rat group on a calorie restricted rat SAD diet.

As for Mitochondria, I do not fully understand this, perhaps someone who has a background in Biochemistry such as @richard could chime in. Anyone know if any of the Keto docs such as Dr. Fung have commented? The 2008 article seems to imply that within the limited scope of what they are analyzing as @OldDoug pointed out, heart muscle seems to prefer a mix of glucose and ketones. It sounds like that group of participants was not the healthiest in terms of their hearts to begin with. However, in general Afib can affect younger healthier people and seems to affect a lot of athletes which is surprising given that exercise is supposed to be healthy.

As for cultures thriving on the keto diet, I would like to believe that an indigenous Alaskan native has similar genetics to someone from southern Europe for example but given what we are learning about epigenetics I am wondering if that is true or if there is some adaption (yes I am familiar with the experiments at Bellvue in the 1920s where the explorers ate whale blubber for a year in a locked ward).

I would love for this study to be wrong. Nothing would make me happier. However Afib is a big deal and frankly as between prediabetes and Afib I would rather have prediabetes. Since Afib is not constant it is not the easiest to detect and shows up in populations you would not expect such as pro athletes After reading the study my first reaction was to go out and buy one of those Fitbits that can detect Afib (talked myself out of that for now). Frankly the Warferin commercials scare me since the people they show are relatively young and healthy looking who made their money running, biking or with a club or a ball. Bottom line, if someone already has health problems or cancer that keto can help, there probably is a benefit that outweighs the risks as the article noted. However for someone who is perfectly healthy and has adopted Keto as a lifestyle, I would like some reassurance


(Bacon by any other name would taste just as great.) #14

It was 1927, and they didn’t eat whale blubber, just meat and fat from butchers in New York. I don’t know about Anderson, but Stefansson continued his meat-only diet till the end of his life. He and his wife retired to a small village in New England, and he said he was grateful that no one else liked fat as much as he did, because the butcher would give it to him almost for free.

There is a fascinating television interview with Stefansson done by the CBC available on YouTube. His widow’s reminiscences are also available on YouTube.


#15

I know! It was simpler to say it that way! I figured the post was already too long

One of my personal problems with Keto is that I hate meat based fat, it makes me gag, always has. Same with my mother and according to what I heard, my grandfather as well. My husband loves it so I trim mine and give it to him


#16

WAY too many people have been eating LCHF and Keto for years and decades and thriving, don’t let a half assed study scare you. Go by how you feel, do labs 1-2 a year and feel confident. My old doctor was a mainstream MD… so he sucked. I used that to my advantage. Couple years ago when everybody here was getting CAC’s and LipoProfiles I was like “Hey, I want that”, and they’re not expensive but I didn’t want to pay either. Told my doc I was doing keto for 2yrs at the time and should I be checked for anything and what he though… “You’re what”? Got every test under the sun LOL!

My new doc (functional) is like… COOL! Remember, eating this way has been under attack since Atkins, it’s never going to change. Keto is a bout as mainstream as it’s ever going to get at this point and it’s loosing it’s fad status, another couple years people won’t go out of their way to tell people who know better how bad it is for you.


(Central Florida Bob ) #17

Not to be rude, but those are commercials. They use good looking young, healthy people because (as my Father-in-law used to say) “if I wanted to see ugly people I’d go ride the city bus”. Did you ever notice that they sell drugs for rheumatoid arthritis with the same beautiful, young people with perfectly straight and healthy looking fingers, not with their fingers at bad angles like people who actually have RA?

Exercise can kill you. I know somewhere around here I’ve posted about this book. Probably several times.

As a culture, Americans seem to have the mindset that “if a little is good a lot must be better.” No. Just no. Think of a medicine where too little doesn’t affect the condition and too much kills you.


(Bob M) #18

Keto doesn’t have to be high fat. If you don’t like fat, that’s not a problem. I commonly eat ham (very low fat, just buy ones that are lower in carbs), top round/london broil, which is beef that’s low in fat, etc.

7.5+ years ago (while on SAD), I developed idiopathic dilated cardiomyopathy. Basically, my heart was getting bigger and they don’t know why. (My theories: stress, too much alcohol, possibly PUFAs.) Part of the issue I had included arrhythmia.

After 7+ years low carb/keto (and some drugs), I have corrected my heart size, and have little to no arrhythmia. Still have them every once in a while, though.

But I would say that if you look into heart failure (technically what I have), you will find that the failing heart loves ketones. Given this is true, it’s highly unlike “keto” would cause Afib.


(Central Florida Bob ) #19

I should probably mention my own story. Just turned 67 this month. Back in '13, on the day I turned 59, my wife and I were low carb but not keto. Since it was my birthday we said we’d do a cheat day and IIRC she made me a carrot cake. No problems, life as usual. Until the next day.

The next morning, I’m in a bathroom stall at work and suddenly had a feeling like an impact hitting the middle of my chest. I take my pulse and it’s 34. I didn’t pass out, didn’t have chest pains, didn’t have arm pains. It eased up and I went back to my office. A couple of hours later, I started having different weird sensations in my chest, but not like getting hit, so I left work and went to the doc in a box. By that time I felt normal and my EKG was normal.

It took two weeks to get into see the cardiologist for the overnight Holter monitor and for the two weeks I continued to have palpitations and weird feelings several times a day but not constantly. They told me I had just about every weird rhythm there is, including AFIB, put me on a beta blocker and had me get an echocardiogram and a nuclear stress test (God, I love that name!). By that time, I had resumed feeling pretty normal. The tests showed nothing, really.

I started watching my electrolytes closer, upped my magnesium. At the time, it was the cheap MgO; a couple years ago, I switched to Magnesium Glycinate, for its better absorption (as I read).

That was '13. I went fully keto in the spring of '15 and I don’t recall having any issues between '13 and then. Some time around mid-'16, I woke up in the middle of the night with the palpitations and weirdness. I had a repeat of the nuclear stress test and echocardiogram. Again, nothing abnormal enough for them to react to. There might have been three or four times since '13 that I’ve felt that. I still see the cardiologist once a year.

Like you said, @Saphire, I’d rather have prediabetes than Afib, and I’d rather have just about anything than a bad stroke. I know people from many backgrounds who have had Afib. It’s correlated with diabetes, too. Nobody I know with Afib has had a stroke. Three have had the ablation procedure, one of them had it twice to fix it.


(Bob M) #20

@CFLBob Interesting background! You might also consider magnesium orotate. I take this sometimes, though I also take many different mgs (mg taurate, for instance):

One thing people on keto should do is adjust electrolytes, particularly salt, though magnesium and even potassium can be issues. I’ve been doing this for a long time, and still can’t figure out exactly how to do this, though…

I personally think things like PUFAs and even very long bouts of exercising (or both) can damage the heart.